2,6-Lutidine, alkylation

In the absence of an added solvent, 3-alkyIpyridines, 4-alkyl-pyridines, and 3,4-dialkylpyridines all gave yields of substituted 2,2 -bipyridines that were up to three times greater than that of 2,2 -bipyridine from pyridine under similar conditions. With 3-ethyl-4-methylpyridine a marked improvement in yield was ob.served when the reaction was carried out at about 150°C in a vacuum, rather than at the atmospheric boiling point (195°C) of this base. This effect has also been observed with some other bases but the amount of 3,3, 5,5 -tetramethy 1-2,2 -bipyridine from 3,5-lutidine could not be increased in this way, and this pyridine was as unreactive as the 2-substituted pyridines. This finding is undoubtedly related to the reluctance of 3-substituted pyridines to form 3,3 -disubstituted 2,2 -bipyridines. 

Methylpyridines (picolines) and dimethylpyridines (lutidines) have prominent m/z 65 and m/z 66 ions in their mass spectra. Aniline can be distinguished from picolines by the m/z 78 ion in the mass spectra of picolines. If the alkyl group. R. is attached to the carbon atom adjacent to the nitrogen atom. RCN can be lost easily. Alkylpyridines are characterized by ions at m/z 65, 66, 78, 92, 106, and so forth. 

Jiang et al.4 have recently succeeded in hydrogenating both aryl alkyl and dialkyl ketones. High enantioselectivity was obtained using PennPhos (19)-coordinated Rh complex as the catalyst. This success is based on the finding that a weak base (such as 2,6-lutidine) can facilitate the Rh-catalyzed hydrogenation of simple ketones (Scheme 6 35). 

Treatment of the alcohol 211 with f-butyklimethylsilyl triflate and 2,6-lutidine affords disiloxyester 212 with high yield. Reduction of the ester function of 212 with DIBAL followed by Swern oxidation gives the corresponding aldehyde 213, and subsequent alkylation with MeMgBr and Swern oxidation produce methyl ketone 214 (Scheme 7-70). 

Aromatic N-containing heterocycles (pyridine, imidazole etc.,) and their alkyl derivatives represent an important group of products and they have received considerable attention because of their various applications. For instance, methyl pyridines (picolines) and dimethyl pyridines (lutidines) are a class of industrially valuable compounds for the production of dyes and fine chemicals [108]. Sreekumar et al [109] reported pyridine methylation to 3-picolines over Zni xCoxFe204 spinel systems at reaction temperature between 325 and 425°C. The... 

Aliphatic Ketones The asymmetric hydrogenation of simple aliphatic ketones remains a challenging problem. This may be attributed to the difficulty with which the chiral catalyst differentiates between the two-alkyl substituents of the ketone. Promising results have been obtained in asymmetric hydrogenation of aliphatic ketones using the PennPhos-Rh complex in combinahon with 2,6-lutidine and potassium bromide (Tab. 1.11) [36]. For example, the asymmetric hydrogenation of tert-butyl methyl ketone affords the requisite secondary alcohol in 94% ee. Similarly, isopropyl, Butyl, and cyclohexyl methyl ketones have been reduced to the corresponding secondary alcohols with 85% ee, 75% ee, and 92% ee respectively. 

The most common synthesis of sulfonic esters, which can also be conducted on insoluble supports, is the sulfonylation of alcohols with sulfonyl chlorides under basic reaction conditions. Several examples of the sulfonylation of support-bound alcohols and of the reaction of support-bound sulfonyl chlorides with alcohols have been reported (Table 8.11). For the preparation of highly reactive sulfonates, bases of low nucleophilicity, such as DIPEA or 2,6-lutidine, should be used to prevent alkylation of the base by the newly formed sulfonate. This potential side reaction is, however, less likely to occur on cross-linked polystyrene than in solution, because quaternization on hydrophobic supports only proceeds sluggishly (see Section 10.2 and [155]). 

Reactions with Acyl Halides. The palladium-carbon bond in alkyl VII and acyl VIII complexes also can be broken by acyl and alkyl halides, respectively, to give ketones (55). The reaction of the benzyl complex Vila with acetyl chloride in the presence of 2,6-lutidine provided good yield of methyl benzyl ketone, XVII. In the absence of the base, lower yields (26% ) were obtained. Surprisingly, a similar reaction between the benzyl complex and an excess of phenylacetyl chloride afforded a 156% yield of dibenzyl ketone, XVIII, based on the starting benzyl complex (see bottom of p. 105). 

Trivial names for the methylpyndines are the picolines the dimethyl-pyridines are the lutidines-, and the trimethylpyridines (and in older literature the ethyldimethylpyndines) are the collidines. The refractive indices foi these alkyl pyridines and for pyridine itself fall in the range nD20 1-50-1.51. 

Reduction of the isomeric lutidines was also studied (Scheme 6).34,46,47 In some cases the products were only cis as in reduction of 2,6-lutidine (20), and in other cases the products were mixtures of stereoisomers, as in 2,3-lutidine (21). When alkyl substituents were in the 3,4- or 3,5-positions, piperideine products were predominant (Table II). Reduction of the symmetrical collidine (13) gave various piperidine isomers of which the all-cis (22) was predominant48 However, the 3-olefin 23 was the major product. The theormodynamically less stable piperidines 24 and 25 were found in significant yield. 

Conjugate addition of RBr to a, -enoates. A Ni(0) catalyst formed from NiCl2-6H20, zinc (2 equiv.), and pyridine can effect addition of alkyl bro-mides(iodides) to electron-deficient C-C double bonds. A wide range of organic halides can undergo this reaction. A trace of water is necessary for turnover numbers of 20 or more. A number of bases can replace pyridine a-picoline, 2,4-lutidine, DBU but not TMEDA or 2,4,6-collidine. 

A synthesis of the immunosuppressant Sangltfehrin by Duan and Paquette featured the cleavage of a phenolic rerf-butyl carbonate using TMSOTf and 2.6-lutidine without complication from alkylation of the phenol ring by rerf-butyl cation [Scheme 4.3551.674... 

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